Jurnal Skizotipal 3

www.nature.
com/npjschz
REVIEW ARTICLE OPEN
Diagnosis and treatment of schizotypal personality disorder:

evidence from a systematic review
Sophie K. Kirchner1, Astrid Roeh1, Jana Nolden1 and Alkomiet Hasan1
The main objective of this review was to evaluate studies on the diagnosis, treatment, and course of schizotypal personality
disorder and to provide a clinical guidance on the basis of that evaluation. A systematic search in the PubMed/MEDLINE databases
was conducted. Two independent reviewers extracted and assessed the quality of the data. A total of 54 studies were eligible for
inclusion: 18 were on diagnostic instruments; 22, on pharmacological treatment; 3, on psychotherapy; and 13, on the longitudinal
course of the disease. We identified several suitable and reliable questionnaires for screening (PDQ-4+ and SPQ) and diagnosing
(SIDP, SIDP-R, and SCID-II) schizotypal personality disorder. Second-generation antipsychotics (mainly risperidone) were the most
often studied drug class and were described as beneficial. Studies on the longitudinal course described a moderate remission rate
and possible conversion rates to other schizophrenia spectrum disorders. Because of the heterogeneity of the studies and the small
sample sizes, it is not yet possible to make evidence-based recommendations for treatment. This is a systematic evaluation of
diagnostic instruments and treatment studies in schizotypal personality disorder. We conclude that there is currently only limited
evidence on which to base treatment decisions in this disorder. Larger interventional trials are needed to provide the data for
evidence-based recommendations.
npj Schizophrenia (2018)4:20 ; doi:10.1038/s41537-018-0062-8
INTRODUCTION Since the introduction of the diagnosis of STPD in Diagnostic

Schizotypy is a heterogenous syndrome that is expressed across and Statistical Manual of Mental Disorders, Third Edition (DSM-III)
multiple dimensions, including cognitive-perceptual, disorganized, in 1980, the diagnosis and treatment of STPD have remained
and interpersonal symptoms1 or according to the symptomology difficult because of the lack of evidence-based algorithms. The
of schizophrenia, positive, negative, and disorganized factors.2–4 original STPD item set was derived from the criteria of borderline
schizophrenia seen in the relatives of schizophrenia patients. The
Raine1 described two types of schizotypy: (1) neurodevelopmental
differentiation between schizotypal traits and STPD is clinically
schizotypy with relatively stable traits and significant brain and
important and reflects the degree of impairment in occupational
neurocognitive impairments that predispose to schizophrenia, and and interpersonal functioning and the severity of symptom
(2) pseudoschizotypy, a pronounced psychosocial entity with presentation.14 This review focuses on the diagnosis of and
more symptom fluctuation that is unrelated to schizophrenia. therapeutic approaches in patients with a disease severity that
Schizotypy, as a broader collection of both clinical and nonclinical fulfills the criteria of STPD not only as a premorbid condition or
traits, is assessed by psychometric inventories such as the risk state but also as a separate diagnostic entity.
Wisconsin Scales of Schizotypy.3 The assessments for schizotypal For years, the International Classification of Diseases (ICD) from
traits are mainly used to define a high-risk group and its the World Health Organization (WHO) and other classification
proneness to psychosis.5 Mason described 16 different schizotypy instruments, e.g., the DSM from the American Psychiatric
scales that were based on clinical concepts or definitions and six Association (APA), have differed in their classification of STPD
scales for psychometric/personality measures of schizotypy.5 (referred to as schizotypal disorder in the ICD): In ICD-9 and -10, it is
According to the theoretical models of Meehl,6,7 Lenzenweger,8 listed under schizophrenia spectrum disorders, whereas in DSM-III
Chapman,9 and Kwapil,10 schizotypy is a premorbid condition. The to -5 it is classified as a personality disorder. In the forthcoming
term schizotypy refers to both people with schizotypal personality ICD-11, it will remain in the block of schizophrenia spectrum
disorder (STPD) and healthy individuals in the general population disorders.15 In DSM-5, a diagnosis of STPD is defined by the
with certain personality traits and a latent liability for psychosis.1 following symptom categories: (1) general impairments in
personality and self-functioning (identity and self-direction) and
Consequently, research has been performed in both clinical
in interpersonal functioning (empathy, intimacy); (2) STPD-specific
patients and healthy schizotypal individuals. Several authors argue
pathological personality traits, described as psychoticism, eccen-
for a dimensional approach and a continuum between schizotypal tricity, cognitive and perceptual dysregulation, and unusual beliefs
traits and schizophrenia spectrum disorder1,11,12; support for their and experiences, (3) detachment characterized by restricted
argument is provided by genetic and linkage studies showing a affectivity and withdrawal, and (4) negative affectivity character-
considerable overlap between genetic association profiles in ized by suspiciousness. In ICD-10,16 and very likely in ICD-11,
schizotypy and schizophrenia.13,14 however, schizotypal disorder (F21) is characterized by eccentric
1
Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany
Correspondence: Sophie K. Kirchner (SophieKathrin.Kirchner@med.uni-muenchen.de)
Received: 5 November 2017 Revised: 15 August 2018 Accepted: 21 August 2018
Published in partnership with the Schizophrenia International Research Society

Diagnosis and treatment of schizotypal personality disorder:. . .
SK Kirchner et al.
2
behavior and changes in thinking and affect similar to those in sharper discrimination between STPD and related PDs, such as
schizophrenia; the evolution and course of the disease resemble BPD and schizoid PD.30 In the evolution of the ICD system, the
those of a personality disorder (PD). threshold for meeting symptom criteria was also crucial for
The prevalence of STPD has been described as ranging from differential diagnosis: Whereas in ICD-8/-9 less patients would
0.6% in a Norwegian sample to 4.6% in an American sample.17 have been diagnosed with STPD, in ICD-10 the threshold was
Men (4.2%) are more often affected than women (3.7%).17 lowered and more patients were diagnosed with STPD. In the ICD
Common differential diagnoses are other PDs such as the system, the severity of the disease may mark the discrimination
borderline personality disorder (BPD), attention-deficit disorder between STPD and schizophrenia, which would favor a dimen-
(inattentive type), social anxiety disorder, autism-spectrum dis- sional diagnosis concept.31 Most of the studies evaluated the
order, and dysthymia.18 Comorbidities can complicate the disease inter-rater reliability (which ranged from 0.62 to 0.91) and
course and treatment responses, and several studies focus on test–retest reliabilities (which ranged from 0.64 to 0.84) of the
interventions for patients with comorbid obsessive-compulsive diagnostic instruments; reliabilities were adequate (see Table 1).
disorder (OCD)19 and BPD. Schizotypy occurs more often in Among the diagnostic instruments, three were identified as being
relatives of patients with schizophrenia or a Cluster A PD. Twin suitable for diagnosis because they had adequate reliabilities and
studies showed highly stable genetic factors and rather transient validities for the respective diagnostic criteria: the Structured
environmental factors for an increased risk for the schizotypal Interview for DSM-III Personality Disorder (SIDP),33 the Semi-
syndrome,20 and genetic risk variants for schizophrenia could also structured Interview for DSM-III-R Personality Disorders (SIDP-R),35
be linked to STPD.21–23 The conversion rates from STPD to and the Structured Clinical Interview for DSM-IV (SCID-II)37 (see
schizophrenia spectrum disorders vary between 20 and >40%, Table 1). The self-report instruments Schizotypal Personality
depending on the follow-up interval.1,24 Imaging studies detected Questionnaire (SPQ) and Schizotypal Personality Questionnaire—
numerous group-level differences in the size of specific brain Brief (SPQ-B) were designed as screening instruments for STPD.
regions in individuals with STPD or schizotypy in comparison with The SPQ-B shows adequate internal consistency (coefficient
healthy participants, patients with schizophrenia, and patients kappa = 0.87),42 and the SPQ shows strong correlations between
with other PDs.18 patients’ responses and SCID-II–rated symptoms.38,43 The Person-
Despite these research efforts, evidence-based recommenda- ality Diagnostic Questionnaire-4+ (PDQ-4+) is also a self-report
1234567890():,;
tions are still lacking for the diagnosis and treatment of STPD. instrument for diagnosing PD. It has more false-positive results
National and international treatment guidelines for schizophrenia than the SCID-II and is therefore only useful as a screening tool for
spectrum disorders (e.g., from the APA, the National Institute for PDs but not as a diagnostic tool.44 The Minnesota Multiphasic
Health and Care Excellence and World Federation of Societies of Personality Inventory (MMPI) could not differentiate between
Biological Psychiatry (WFSBP)) do not discuss this topic, and individuals with STPD and schizophrenia.45 However, a distinct
specific guidelines for personality disorders pay only little profile (MMPI 2-7-8) showed an enrichment of diagnoses of
attention to STPD.25 Rosell et al.18 recently published a non- Cluster A PDs when compared with SIDP-IV interviews. None of
systematic literature review on the epidemiology, functional the instruments was designed to evaluate disease severity. Three
impairment, heritability and genetics, cognitive impairments, studies compared diagnostic interviews with factor analysis
social-affective disturbances, and neurobiology of STPD. This models.35,40,44 According to Battaglia et al.35, the three factors
detailed review provides a deeper insight into the pathophysiol- cognitive-perceptual, interpersonal, and oddness best describe
ogy of and experimental research on STPD and includes the diagnosis of STPD; Fossati et al.37 made the same statement,
information on imaging and genetic and psychological testing.18 but these two studies had overlapping patient cohorts. Sanislow
Nevertheless, it remains unclear which diagnostic tools, medica- et al.40 developed a four-factor model and argued that it was
tion, or psychotherapy are recommended. Therefore, the main significantly better than the established unitary “generic” model.40
objective of this systematic review, which was based in principle Please see Table 1 for details.
on the recommendation of the Preferred Reporting Items for
Systematic Reviews and Meta-Analyses group,26 was to evaluate Articles on interventional drug treatment trials
the literature on the diagnosis and treatment of patients seeking
Study characteristics. Most of the studies were prospective
help for STPD. In addition, it offers some information on the
double-blind, placebo-controlled trials,46–56 and all publications
longitudinal course of STPD and conversion rates to other
reported single-center results. We also identified one double-
schizophrenia spectrum disorders.
blind, treatment-controlled trial;57 one single-blind, placebo-
controlled trial;58 four open-label trials;59–62 one retrospective
RESULTS study;63 and four case reports.64–67 Please see Table 2A, B and
Supplementary Table 3 and 4 for further study details and level of
Articles on diagnostic instruments
evidence (LoE) grading. In total, 16 individual drug treatments
Study characteristics. When examining the articles on diagnostic were studied. The most frequently studied drug was risper-
instruments, we focused on studies that tested disease criteria27– idone,50,53,54,62 and the most frequently studied class of drugs
31
and clinical diagnostic questionnaires for STPD.32–39 One study were the antipsychotics,47,48,50,53,54,57–60,62,63,66 followed by the
did not specifically evaluate a diagnostic questionnaire but antidepressants.46,61,64,65 Six studies tested other neuroactive
compared a factor analysis model with established drugs.49,51,52,55,56,67 In most studies, the main outcome measure-
questionnaires.40 ment was a general psychiatric symptom scale, such as the Brief
Psychiatric Rating Scale,60,63,67 the Hopkins Symptom Check-
Individual outcomes. Five studies aimed at evaluating the list,48,61 and the Psychiatric Assessment Interview.57 Three trials
variables of the diagnostic criteria, the shifts in diagnosis from used interviews for specific psychotic symptoms, such as the
DSM-III to -5 or ICD-8 to -10 and their effect on diagnostic Positive and Negative Symptom Scale (PANSS).50,53,56 Some
sensitivity, specificity, and diagnostic overlap,27,28,30,31,41 as indi- studies focused on patients with comorbidities of OCD or BPD
cated in Table 1. The reliability of the DSM-III criteria had an and consequently measured outcome with the Yale-Brown
adequate mean kappa of 0.71.27 In DSM-III, the diagnoses of BPD Obsessive Compulsive Scale (YBOCS)46,48,59,66 or the Self-
and STPD interacted on the symptom level.27 In DSM-III-R, the Injurious Behavior scale.47 One study used a specific tool, the
threshold for an STPD diagnosis was raised, and the number of SPQ, to assess the severity of STPD as an additional outcome
STPD diagnoses consequently decreased by 40%. This offered a measurement tool.50 Common secondary outcome tools were
npj Schizophrenia (2018) 20 Published in partnership with the Schizophrenia International Research Society
Table 1. Qualitative synthesis of diagnostic instruments for schizotypal personality disorder
Reference Study population Questionnaire Outcomea
Perry et al.34 ntotal = 19 psychiatric patients Schedule for Schizotypal The SSP is a structured interview developed by Baron for identifying relatives of chronic
Personalities (SSP), DSM-III schizophrenic patients. Here it is tested if the SSP is also suitable for clinical patients.
symptom criteria The reliability coefficients of the statement scores for the SSP range from IR = 0.68 to
0.99. Using the score from the SSP, the inter-rater reliability of making a diagnosis of SPD
was IR = 1.0. Using the author’s individual ratings for making clinical diagnosis of SPD,
the IR was 0.72. The reliability for the single items was found reliable and valid with the
exception of odd speech. The retest reliability for the SSP of the SPD diagnosis was IR =
0.84. The retest reliability for the authors’ consensus diagnoses was not obtained. The
authors’ clinical consensus was used as the criterion for determining the validity of the
diagnosis: The validity of the SSP depends on the cutoff for symptom criteria. At the
cutoff of 2 criteria, the diagnostic sensitivity is 100% and the specificity is 9%. At the
cutoff of 4 criteria, the diagnostic sensitivity decreased to 13% and the specificity rose to
100%. For the evaluation of the diagnostic validity of the DSM-III criteria, the authors’
consensus judgement was compared with the diagnosis based on DSM-III criteria. The
sensitivity per item ranges between 25 and 88% (except for the criterion recurrent
illusion) and the specificity is for all items >80%. The authors recommend combining
the criteria in four conceptual categories: (a) self-report of cognitive-perceptual
disturbances, (b) observable disorder of thought/communication, (c) deficits in drive/
affect, and (d) interpersonal difficulties
Stangl et al.33 ntotal = 131 psychiatric patients, Structured Interview for DSM-III The SIDP is a semi-structured interview. It is designed to assess the DSM-III-R PD
nPD = 67, nSPD = 12 Personality Disorder (SIDP) diagnoses. It was developed to improve Axis II diagnostic reliability. 63 patients were
retested and rated by two raters. The kappa coefficient for SPD was 0.62. The authors
argue that the validity cannot be measured since the SIDP is based on the DSM-III
criteria. The DSM-III criteria have not been tested for validity and another gold standard
is missing

Jacobsberg et al.27 ntotal = 64 psychiatric patients, DSM-III criteria, Global Assessment The reliability for identifying schizotypal symptoms by DSM-III criteria showed a mean
nSPD = 35 Scale (GAS), Schedule for kappa = 0.71. Patients with schizotypal personality disorder showed a lower GAS score
Interviewing Borderline Patients than patients with other personality disorders. In this clinical sample, DSM-III symptoms
of schizotypal and borderline personality disorder interact. The following symptoms
were significantly related with the diagnosis of schizotypal personality disorder
SK Kirchner et al.
compared to other personality disorders: inadequate rapport (φ = 0.61), odd

communication (φ = 0.54), chronic boredom (φ = 0.48), depersonalisation (φ = 0.45),
social isolation (φ = 0.45), illusions (φ = 0.44), ideas of reference (φ = 0.38), identity
disturbance (φ = 0.33), undue mood elevation upon praise (φ = 0.33),paranoid ideation
(φ = 0.32), magical thinking (φ = 0.32), compulsive sociability (φ = 0.28), and delusions
(φ = 0.27). Patients with schizotypal diagnosis vary in their symptoms depending on
whether these patients have been drawn from clinical or familial samples
Widiger et al.28 ntotal = 84 psychiatric patients DSM-III criteria The internal consistency and descriptive validity of the borderline and schizotypal
symptoms were analyzed by calculating (a) their sensitivity, specificity, positive
predictive power, and negative predictive power, and (b) their correlation with the
diagnoses’ cutoff points and total number of symptoms. Most of the symptoms were
successful as inclusion tests but not as exclusion tests. The social-interpersonal
symptoms were less efficient in differentiating schizotypal from borderline patients
than the perceptual-cognitive symptoms. The schizotypal symptom combinations had
consistently high positive predictive power (PPP) rates. None was <0.81, with the
exception of social anxiety-hypersensitivity and social isolation, which obtained a PPP of
only 0.73. The means of the PPP and specificity rates for SPD were 0.92 (SD = 0 .07) and
0.95 (SD = 0.06) and the mean negative predictive power (NPP) and sensitivity rates for
SPD were 0.53 (SD = 0.04) and 0.39 (SD = 0.11)
npj Schizophrenia (2018) 20

McGlashan29,41 ntotal = 109 psychiatric patients DSM-III symptom criteria The most characteristic symptoms for schizotypal personality disorder are odd
(SPD and/or BPD), nSPDonly = 10 communication, suspiciousness/paranoid ideation, and social isolation. The least
3
4
Table 1 continued
discriminating symptoms are illusions/depersonalisation/derealisation. Whereas

depression as a symptom does not discriminate between SPD and BPD, transient
psychoses and brief paranoid experiences fit better as SPD criteria
Vaglum et al.30 ntotal = 97 psychiatric patients, DSM-III and DSM-III-R criteria The inter-rater reliability is for DSM-III and DSM-III-R equally good (kappa value for DSM-
nSPD = 21 (by DSM-III rating), III diagnosis is 0.64 and for DSM-III-R of 0.67). When diagnosed by DSM-III-R criteria, the
nSPD = 13 (by DSM-III-R rating) number of SPD diagnosed was reduced by 40% compared to DSM-III criteria. Of the
schizotypal patients, who lost their diagnosis in DSM-III-R (n = 8), 4 got a new diagnosis

of schizoid personality disorder and 4 maintained their comorbid borderline personality
disorder
Raine34 Sample (1): n1 = 302 Preliminary Schizotypal Personality The SPQ is a self-report measure for all nine feature categories of the schizotypal
population-based subjects Questionnaire (SPQ), Present State personality disorder as defined by DSM-III-R. Items for the SPQ were generated from the
used for the development of Evaluation (PSE), Scale for the PSE, SANS, SCID-II, and SADS. Additionally, some items of the STA scale, the Schizotypy
the test Assessment of Negative Symptoms scale, the Perceptual Aberration scale, and the Magical Ideation scale were included. The
(SANS), Structured Clinical SPQ was found to have high internal reliability (0.91), retest reliability (0.82),
Interview for DSM-III-R Personality discriminant validity (0.63), and criterion validity (0.68). 55% of the subjects scoring in
Disorders (SCID-II), Schedule for the top 10% of the SPQ had a clinical diagnosis of schizotypal personality disorder. The
Affective Disorders and authors conclude that the SPQ might be a good tool for screening for schizotypal
Schizophrenia (SADS) personality disorder
Sample (2): n2 = 195 Schizotypal Personality
population-based subjects Questionnaire (SPQ), Structured
used to test the replicability of Clinical Interview for DSM-III-R
results generated in the first Personality Disorders (SCID-II)
sample
SK Kirchner et al.
Battaglia et al.35 n1 = 538 nonpsychotic Italian version of Semistructured The SIDP-R is a structured interview that covers the full DSM-III-R range of PDs. The
psychiatric patients, n2 = 225 Interview for DSM-III-R Personality mean kappa value, chance corrected for SIDP-R-generated Axis II diagnoses, was 0.83;
non-patient controls Disorders (SIDP-R) the mean kappa value for SIDP-R diagnosis of SPD was 0.89. Three factors encompass
the diagnosis best: cognitive-perceptual, interpersonal, and oddness
Merrit et al.36 ntotal = 4000 students, n2-7-8 = Minnesota Multiphasic Personality Participants with a distinct profile on MMPI (2-7-8) received higher scores of personality
38 Inventory (MMPI), Structured disorder diagnoses than controls. 85% of the 2-7-8 group received a Cluster A diagnosis.
Interview for DSM-IV Personality 50% of participants with a 2-7-8 profile received the diagnosis of schizotypal personality
Disorder (SIDP-IV) disorder according to DSM-IV criteria measured by SIDP-IV
Fossati et al.37 ntotal = 564 psychiatric patients, Structured Clinical Interview for The SCID-II is a structured interview for DSM-IV criteria for all personality disorders. The
nSPD = 30 (by SCID-II rating) DSM-IV (SCID II) inter-rater reliability was adequate for all SPD criteria (median kappa = 0.846). SPD is
best explained by four latent classes, but only the latent class I (“no close friends,” odd
thinking,” “suspiciousness,” and “inappropriate affect”) is associated with SPD
diagnosed by DSM-IV. The most discriminating DSM-IV SPD criterion was “odd thinking”
Sanislow et al.40 ntotal = 668 psychiatric patients Structured Clinical Interview for Confirmatory factor analysis was used to test the DSM-IV construct of the borderline,
DSM-IV Axis-I Disorders–Patient schizotypal, avoidant, and obsessive-compulsive disorder. A model based on the three
Version (SCID-I/P), Diagnostic DSM-IV Axis II clusters was also tested. Both models were tested against a unitary
Interview for DSM-IV Personality ‘generic’ model constructed from four criteria sets combined. Median kappa coefficients
Disorders (DIPD-IV) ranged from 0.58 to 1.0 for all Axis II disorders. Based on factor analysis, a one-factor,
three-factor and a four-factor-model were established. The four-factor model provided
an analysis acceptable fit to the data (χ2 (489) = 1756.8; CFI = 0.83, NFI = 0.78 and
RMSEA = 0.062). Overall, results from this study support the division of DSM-IV
personality disorders into at least four disorders over a unidimensional model of
personality disorder (based on the numerous studies documenting high co-occurrence
among DSM-IV personality disorders), and over a three-factor model of personality
disorder (based on the DSM-IV Axis II clusters).
Axelrod et al.42 n = 237 psychiatric patients, Schizotypal Personality The SBQ-B is a self-report instrument. It is modeled after the DSM-III-R schizotypal
nPD = 34 Questionnaire Brief (SPQ-B) personality disorder diagnostic criteria (largely unchanged in DSM-IV). It was developed

to study schizotypal personality patterns and to screen for schizotypal personality
disorder in the general community. It includes cognitive-perceptual deficits,
Table 1 continued
interpersonal deficits, and disorganization. The SBQ-B shows adequate internal

consistency (coefficient alpha = 0.87). The Interpersonal and Cognitive-Perceptual
subscales demonstrates convergent and discriminant relationships with other measures
of interpersonal impairment and cognitive abnormalities. The Personality Disorder
group had significantly greater Interpersonal Deficit scores than the Conduct Disorder
and Substance Use Disorders groups (p < 0.05)
Matsui et al.45 ntotal = 321 psychiatric patients Minnesota Multiphasic Personality Discriminant function analysis of the MMPI profiles revealed significant variance among
and healthy controls, nSPD = 18, Inventory (MMPI) the three groups. The overall rate of correct classification of the subjects into
nSZ = 41, nstudents = 262 schizophrenia, SPD, or university students was 90.3%. Yet, there is a considerable
overlap between schizophrenia and SPD
Dickey et al.38 nSPD = 104 Structured Clinical Interview for Inter-rater reliability for diagnosis of SPD based on SCID interviews of 25 subjects and 3
DSM-IV (SCID II), Schizotypal raters showed a kappa of 0.89. The most common SPD criteria met was impairment due
Personality Questionnaire (SPQ) to experiencing unusual perceptions, followed by suspiciousness/paranoid ideation and
odd beliefs/magical thinking. There were strong correlations observed between SPD
subjects’ self-report on the SPQ and SCID interview for the Cognitive Perceptual (r =
0.616, N = 41, p < 0.0005) and the Interpersonal (r = 0.406, N = 41, p = 0.008) factors but
not for the Disorganized factor (r = 0.003, N = 41, p = 0.99)
Fossati et al.44 Study 1: ntotal = 721 psychiatric Personality Diagnostic The SCID II is a structured interview for DSM-IV criteria for all personality disorders. The
patients, nSPD = 31 (by SCID-II Questionnaire-4+ (PDQ-4+), PDQ-4+ is a forced choice, self-report, 99-item questionnaire designed to measure the
rating), nSPD = 166 (by PDQ-4+ Structured Clinical Interview for DSM-IV PDs. In these samples, schizophrenia-spectrum disorders, mental retardation, or
rating) Study 2: n2 = 537 DSM-IV (SCID-II) DSM-III-R dementia were excluded. The inter-rater reliability for diagnosis of SPD based on SCID II
psychiatric patients, nSPD = 16 Personality Disorders-Revised interviews of 25 subjects and 3 raters was kappa = 9.1. PDQ-4+ seems to predict false-
(SIDP-R), Diagnostic Interview positive results. The factor model shows schizophrenia-related schizophrenia. PDQ-4+
Schedule-Revised (DIS-R) scales do not identify subjects with definite personality disorder diagnoses. Reliability
and predictive power improved when SPD was assessed by semi-structured, direct

interviews that used all nine diagnostic criteria instead of through self-assessments of
some dimensions of schizotypy. Considering SCID-II data, Raine’s three-factor model of
SPD features (Raine et al., 1994) was the best fitting model among those considered in
study 1. Oddness was the factor that most sharply discriminated the SPD latent taxon
from the complement in the clinical subjects of this study. The DIS-R is a diagnostic
interview for Axis I disorders. 16 subjects (3.0%) in study 2 were diagnosed with DSM-III-
SK Kirchner et al.
R SPD; this was similar to the number of SPD subjects in study 1, χ2 (1) = 1.15, p > 0.25. In
line with a previous confirmatory factor analysis, the cognitive-perceptual,
interpersonal, and oddness three-factor model of SPD features was the best fitting
model in this sample. The sample of Study 2 has already been explored by Battaglia
et al.35.
Study 3: n3 = 225 non-patient DSM-III-R Personality Disorders- SIDP-R is a semi-structured, 160- item interview divided into 16 thematic sections; it is
controls, nSPD = 2 Revised (SIDP-R) designed to assess the DSM-III-R PDs.
Handest et al.31 ntotal = 151 psychiatric patients, ICD-10 criteria, ICD-8/9 criteria, If the ICD-10 criteria threshold was lowered or elevated, the number of individuals
nSPD = 50 Operational Criteria for Psychotic diagnosed with schizotypal disorder would vastly differ (from 14 to 86 patients in this
Illness (OPCRIT), Bonn Scale for cohort). Factor analysis resulted in four factors: interpersonal/negative, disorganized,
Assessment of Basic Symptoms perceptual/positive, and paranoid symptoms. Compared to the schizophrenia
(BSABS), Positive and Negative subgroup, schizotypal patients scored higher on depression (OR = 6.65, 95% CI
Syndrome Scale (PANSS), DSM-IV 2.52–17.60) and sleep disturbances (OR = 4.91, 95% CI 1.65–14.57) and lower on
Global Assessment of Functioning suspiciousness (OR = 0.28, 95% CI 0.12–0.63), loss of role functioning (OR = 0.17,95% CI
Scale (GAF-F) 0.06–0.44), and odd behavior (OR = 0.42,95% 0.19–0.95). If diagnosed by the ICD-8/9
criteria, only 37 patients (out of 50) would have been diagnosed with schizotypal
disorder. The other 12 patients would have been diagnosed with schizophrenic disorder
by the ICD-8/9 criteria. The severity of psychosis marks the distinction of schizophrenia
from schizotypy. The study shows the arbitrary nature of the four criteria needed for the

ICD–10 schizotypy diagnosis. Schizophrenia and schizotypy are similar on most
psychopathological dimensions
5
SK Kirchner et al.
6
coherence, discrimination, relations with personality traits, and functional impairments.
an average trait–disorder correlation of 0.52. The DSM-5 alternative model features are
The PID-5 is a self-report questionnaire based on DSM-5 criteria. The PDQ-4+ is a forced
patients were additionally rated by clinicians on a four-point trait rating scale. The trait
Schizotypal PD items met three of the four criteria but showed no relation to Five Factor
demonstrated substantial correlations with the corresponding DSM‐IV diagnoses, with

For SPD, the SCID-II showed a convergent validity of 0.64, divergent validity of 0.45, a
roughly comparable with DSM-IV criterion-derived diagnoses with the κs (median κ =

measurements for global functioning, i.e., the Global Assessment
choice, self-report, 99-item questionnaire designed to measure the DSM-IV PDs. The
0.50) obtained when comparing DSM-IV criterion-derived diagnoses with the global
of Symptoms60 and Clinical Global Impression,50 or for depressive
DSM-IV clinical diagnoses made by these same clinicians. The diagnostic rules for
The SCID-II PD items were evaluated for all personality disorders with respect to
schizotypal personality disorder include three traits of the psychoticism domain

symptoms, i.e., the Hamilton Rating Scale for Depression.46,50,62 Six
relation to personality dimension of 0.18, and a relation to impairment of 0.36.
assignments specified for personality disorders in the DSM-5 alternative model
(cognitive and perceptual dysregulation, unusual beliefs and experiences, and

studies had cognitive measures, i.e., working memory,49,52,55
Model of Personality dimensions, suggesting that it may be a candidate for

context processing,51 reaction time,54 response inhibition,54 or a
combination of different cognitive categories,53 as a primary or
eccentricity), which demonstrated correlations between 0.67 and 0.61

secondary outcome.
Individual outcomes. Most of the studies on an antipsychotic

drug intervention found a positive effect in STPD (see Table 2A).
Thiothixine reduced general symptoms (especially illusions, ideas
of reference, paranoid ideation, cognitive deficits, and anxiety) in
cohorts of mixed BPD and STPD patients, but the respective
studies found no significant relationship between diagnosis and
outcome of treatment.47,57 Risperidone was the only drug that was
evaluated in studies that fulfilled relevant study quality criteria,
such as reporting effect sizes, being randomized, and using
quantitative measures and standardized questionnaires. It was
evaluated in four independent studies: Koenigsberg et al. showed
a reduction in the PANSS score in STPD but no difference in the
STPD-specific SPQ;50 Rabella et al. reported an improvement in
reaction time after treatment with risperidone;54 McClure et al.
reassignment to Axis I
found no beneficial effect of risperidone in either the PANSS or

cognitive measurements;53 and the open-label study by Ryba-
kowski et al. found an increase in social and occupational
functioning and cognitive tests after risperidone treatment.62 In
an open-label augmentation trial, a small cohort (n = 11) of
Outcomea
patients with STPD had significant improvements in psychosis and

depression ratings when treated with olanzapine.60 In an open-
label study in patients with comorbid OCD and STPD, a
combination of fluvoxamine and olanzapine showed beneficial
Clinical Interview for DSM-IV, Axis I
effects, i.e., it reduced the YBOCS score,59 and the concomitant

Questionnaire-4 (PDQ-4) for DSM-
(SCID-II), Revised NEO Personality
Assessment of Functioning (GAF)

Inventory (NEO PI-R), Structured
Personality Inventory for DSM-5

Structured Clinical Interview for
diagnosis of STPD was significantly associated with a positive

(PID-5), Personality Diagnostic
DSM-IV Personality Disorders
response. In a retrospective study, Di Lorenzo et al. reported a

Disorders (SCID-I), Global
decrease of general symptoms when patients with schizophrenia

spectrum disorder were treated with aripiprazole; patients with
STPD were included, but no specific results were mentioned.63 In
one case report, clozapine treatment reduced symptoms in a
The descriptions of outcome are direct citations or extracts from the referred publications
Questionnaire
patient with comorbid OCD and STPD.66 Three studies investigat-

ing the use of antipsychotics analyzed mixed cohorts of STPD and
BPD patients,47,48,57 and one study analyzed patients with
schizophrenia spectrum disorder.63
IV
Studies evaluating antidepressant treatment examined only

mixed (BPD and STPD) or comorbid (OCD and STPD) cohorts (see
ntotal = 203 psychiatric patients,
Table 2B). In an open-label trial of fluoxetine, Markovitz et al.

ntotal = 337 patients, nSPD = 32
measured a reduction of general symptoms in patients with BPD,

STPD, or both,61 regardless of the diagnosis. In another study,
clomipramine showed no significant effects on OCD symptoms in
a cohort of patients with OCD and STPD, and the authors reported
Study population
a worse treatment outcome in patients with comorbid STPD than

in those with other PD diagnoses.46 One case report described a
patient with STPD who developed psychotic symptoms after
nPD = 70
treatment with fluoxetine,64 and other case reports showed

positive effects of clomipramine, paroxetine, and buspirone on
depressive or OCD symptoms46,65 (see Supplementary Tables 3C
and D). Five studies tested other substances and their effect on
cognitive impairments in patients with STPD (see Supplementary
Table 3): On the basis of studies showing positive results of
catecholamine agonistic treatment in schizophrenia-related dis-
orders, Siegel et al. tested d-amphetamine in a cohort of patients
with STPD and found an improvement in the Wisconsin Card
Table 1 continued
Sorting Test (WCST); however, the authors found no effect of

symptom change on the PANSS score.56 Two studies tested
Morey et al.39
Ryder et al.43
dopamine agonists (pergolide and dihydrexidine) and showed

improvements in working and verbal memory, executive function-
Reference
ing, information processing, and divided attention.52,55 Two

studies tested modulators of the autonomous nervous system
(intravenous physostigmine, a cholinesterase inhibitor and
a
SK Kirchner et al.
7
enhancer of the parasympathetic nervous system, and guanfacine, Quality of the studies
an α2A receptor agonist and sympatholytic drug) and their effect The composition and size of the cohorts varied greatly across the
on cognition. These studies showed improvements in verbal studies, and all treatment studies were single center. Some studies
memory, visuospatial working memory, and context proces- in mixed samples of patients reported results on very few or only
sing.49,51 The sizes of the studies varied between 1 patient with single STPD patients. It remains questionable whether the results
STPD in a larger mixed cohort63 and up to 31 patients with STPD53 of these studies can be applied to a larger group of patients with
(see Supplementary Table 2). STPD. Most of the articles did not mention disease severity
because of a lack of a suitable measurement tool. A variety of
Articles on psychotherapy methods for evaluating the quality of diagnostic instruments, the
Study characteristics. We identified one randomized clinical trial outcome of clinical interventional studies (drug treatment or
that compared integrated therapy with standard treatment,68 one psychotherapy), or longitudinal outcome were applied across the
uncontrolled clinical trial,69 and one case report of a patient with studies, resulting in a high heterogeneity and hampering
OCD and comorbid STPD.70 The sizes of the studies varied from comparability.
170 to 7968 patients with a diagnosis of STPD (see Supplementary
Table 2).
DISCUSSION
Individual outcomes. An uncontrolled prospective trial of a We present a systematic review of diagnostic instruments and
psychodynamic day-care treatment program found no benefit pharmacological and psychosocial treatment strategies for STPD.
for STPD patients.69 One case report showed a reduction of After performing a standardized and systematic literature search
symptoms in a patient with STPD and OCD70 after social skills and analysis, we assessed 94 full-text articles for eligibility and
training. Another trial also reported a positive effect of social skills evaluated 54 of them. At this point, it would be premature to
training, i.e., STPD patients with this training had a lower transition make clear recommendations for the use of specific diagnostic
rate from STPD to a psychotic disorder.68 We found no trial that instruments or drug or psychotherapy treatment approaches. Our
evaluated cognitive behavioral therapy in STPD (see Table 3). evaluation of diagnostic instruments made clear that the
diagnosis of STPD has changed over time. In each diagnostic
Articles on longitudinal course and follow-up studies system, the threshold for meeting symptom criteria seems to
Study characteristics. We included eight studies of clinical differentiate between related diseases, such as other PDs or
cohorts.71–78 Studies with mixed clinical and non-clinical cohorts schizophrenia. Nearly all the diagnostic instruments discussed for
were included if they predicted the development of an STPD STPD have adequate inter-rater and test–retest reliability. Our
diagnosis from childhood to adulthood or the conversion rate to review confirms that the SIDP for DSM-III, SIDP-R for DSM-III-R, and
psychotic illness.79–81 One article focused of the stability of a SCID-II for DSM-IV are suitable for diagnosing STPD, but we found
diagnosis of STPD in young adult twins.20 The study size that the diagnostic tool PDQ-4+ is more suitable for screening.
depended on the investigated cohort (for details see Supplemen- Factor analysis models are frequently discussed as a diagnostic
tary Table 2). alternative to catalogs with rather arbitrary diagnostic criteria. A
complete review of the scales used to access schizotypy as a
Individual outcomes. The follow-up periods of the studies ranged broad concept can be found in the review by Mason, which
from a minimum of 1 year81 to 27 years.80 In a mixed cohort of focuses not only on the clinical diagnosis but also on psycho-
healthy and mentally ill children, Bernstein et al. showed that an metric measurements that assess schizotypal personality traits and
early STPD diagnosis during adolescence rarely persisted over a 2- define a high-risk group for schizophrenia.5 Longitudinal studies
year follow-up period.79 Along the same lines, in their study in examined the stability of the diagnostic entity and observed
adults Grilo et al. reported a remission of the STPD diagnosis in moderate-to-high remission rates between an early childhood
61% of patients and suggested that, although maladaptive traits onset and later adulthood. Patients suffering of comorbid BPD
may persist, the severity of symptoms can change.76 In contrast, showed poorer social functioning than patients with pure
Asarnow et al. showed that children with a diagnosis of STPD STPD.71,72 Yet, drug treatment responses in patients with
mostly kept the diagnosis, but 25% of them developed more comorbid BPD were regardless of the diagnosis.47,57,61 Patients
severe schizophrenia spectrum disorders (schizophrenia or suffering of a comorbid OCD showed better response rates after
schizoaffective disorder).81 Olin et al. evaluated the relationship treatment with olanzapine59 and poorer responses after clomi-
between personality traits and disorders in a community-based
pramine treatment.46 The articles on treatment clearly showed
cohort of healthy and mentally ill children and concluded that
that antipsychotics are the most frequently used drugs. When we
early traits can be predictive for the development of an STPD. Four
considered only studies that were of acceptable methodological
studies evaluated longitudinal global functioning and impair-
ment:71–74 Impairments in global functioning and social impair- quality (see LoEs in Tables 2 and 3 and Supplementary Table 3 and
ment differed depending on the study sample, but, overall, 4), risperidone had the best, but still limited, evidence for reducing
patients with pure STPD had less impairment than patients with clinical symptoms in patients with STPD. Antidepressants have
other comorbid PDs or SZ. In particular, patients with comorbid only been tested in mixed cohorts (patients with comorbid OCD or
BPD had poor global functioning. Treatment with antipsychotic BPD), making it difficult to draw definite conclusions on their
medication was common in STPD patients.74,75 They were also effectiveness in STPD. Most of the drug treatment studies were
frequently hospitalized and received psychotherapy.75 Two conducted in patients with STPD and a comorbid disorder, which
studies evaluated the stability of symptoms over time: McGlashan also limits our ability to draw conclusions. Moreover, some studies
et al. found paranoid ideation and unusual experiences to be the included only a few patients, resulting in an LoE of 2− to 3.
most stable, whereas oddness appeared to be the least prevalent Remarkably, to the best of our knowledge no treatment guidelines
and most changeable;78 and Kendler et al. studied the stability of or Cochrane Collaboration reviews exist that provide a compre-
Cluster A PDs in twins and concluded that genetic risk factors lead hensive discussion of treatment alternatives for STPD. The WFSBP
to highly stable subtypes of the disorder, whereas shared Guidelines for Biological Treatment of Personality Disorders
environmental risk factors lead to rather transient symptoms20 provide only general recommendations for antipsychotics on the
(see Table 4). Two studies focused on the conversion from STPD to basis of minimal evidence from clinical trials and expert opinion
a psychotic illness and found rates of 25–48%.24,82 (Herpertz et al. 2007).
Published in partnership with the Schizophrenia International Research Society npj Schizophrenia (2018) 20
Table 2. Qualitative synthesis of drug treatment trials 8
(A) Antipsychotics
Reference Study population Study type Inclusion criteria Exclusion criteria Intervention Symptoms Mean Mean Symptom Outcomea Level of
measured pretreatment posttreatment change evidence (risks
of bias LoE
according to
SIGN)
Serban ntotal = 52, 3-month, Diagnosis of BPD or STPD by Schizophrenia or affective disorder Thiothexine Psychiatric Change in The results indicate that properly No
et al.57 nSTPDonly = 14, double-blind, DSM-III criteria, disease hydrocloride Assessment score: mean defined groups of schizotypal and randomization.
nSTPD+BPD = 16 treatment- symptoms >2 years, mild (dose 9.4 ± Interview (for −0.93 borderline patients respond well to Various

controlled trial transient psychotic episode 7.6 mg/day) or nSTPDonly): treatment with tranquilizers, outcomes.
before admission haloperidole general particularly thiothixene. The main Monocentric
(3 ± 0.8 mg/day) symptoms areas of symptom control appear to study. LoE: 2−
(thiothexine be related to general symptoms,
group) cognitive disturbance, paranoid
ideation, anxiety, and depression.
There was no significant relationship
between diagnosis and outcome of
treatment
General Change in
symptoms score: mean
(haloperidole −0.08
group)
Depression Change in
(thiothexine score: mean
group) −0.83
Depression Change in
(haloperidole score: mean
group) −0.68
Paranoia Change in
(thiothexine score: mean
group) −1.28
SK Kirchner et al.
Paranoia Change in
(haloperidole score: mean
group) −0.75
HAMD (for
nSTPDonly)
(thiothexine Change in
group) score: mean
−12.67
(haloperidole Change in
group) score: mean
−10.40
Goldberg ntotal = 50 (BPD 12-week Diagnosis of BPD or STPD by Diagnosis of schizophrenia, mania, Low-dose Global 61.67 72.42 1.16b Significant drug placebo differences No
et al.47 and STPD; 24 in double-blind, DSM-III criteria (rated by and melancholia; severe hepatic, thiothexine Assessment were found, regardless of diagnosis, randomization.
treatment group, placebo- Schedule for Interviewing renal, or cardiovascular disease; hydrocloride Scale (GAS) on “illusions,” “ideas of reference,” Various
26 in placebo controlled trial Borderliners SIB), at least one organic brain symptom and/or (mean dose (for ntotal = “psychoticism,” “obsessive- outcomes.
group), nSTPDonly psychotic symptom mental retardation; history of 8.7 mg/day) 24) compulsive symptoms,” and “phobic Monocentric
= 13 (6 in epilepsy or seizures; glaucoma; anxiety” but not on “depression” study. LoE: 2−
treatment group, current alcoholism or drug addiction;
7 in placebo severe hypertensive or hypotensive
group) cardiovascular disease; severe
metabolic disorders
b
HSCL-90 0.5556 0.2222 0.4823b The symptom change is measured
scale: phobic as standardized change:
anxiety (for (pretreatment score−posttreatment
ntotal = 24) score)/pretreatment standard
deviation
Phobic 0.42 0.16 0.26b
anxiety (for
nSTPD = 6)
Obsessive 1.1429 0.7083 0.504b
compulsive
(for ntotal =
24)
Obsessive 1.38 0.48 0.6b
compulsive

(for nSTPD = 6)
Psychoticism 1.98 0.77 1.21b
(for ntotal = 24)
Table 2 continued
(A) Antipsychotics
of bias LoE
according to
SIGN)
Psychoticism 1.14 0.36 0.73b

(for nSTPD = 6)
SIB
Illusions (for 1.4271 1.2083 0.2715b
ntotal = 24)
Illusions (for 1.25 1.16 0.09b
nSTPD = 6)
Ideas of 1.75 1.1806 0.7463b
reference (for
ntotal = 24)
ideas of 1.72 1.00 0.72b
reference (for
nSTPD = 6)
Schizotypal 15.9062 12.7483 0.7106b
symptoms
(for ntotal =
24)
Psychotic (for 9.1493 7.0937 0.6182b
ntotal = 24)
Hymowitz nSTPD = 17 2-week single- Diagnosis of BPD by DSM-III Axis I diagnosis of schizophrenia or Haloperidole SIB Decline in Patients experienced a decline in No adequate
et al.58 blind placebo- criteria (rated by Schedule for major affective illness (by DSM-III (mean dose total their total schizotypal score. Among concealment
controlled trial Interviewing Borderliners SIB) criteria) 3.6 mg/day) schizotypal the ten individual schizotypal SIB (single-blind).
score (t = scales, ideas of reference, odd No
−2.4401, df = communication, and social isolation randomization.
15, p < 0.05). decreased significantly. The total Various
borderline SIB scores, based on the outcomes.

subsequent 11 SIB scales declined, Monocentric
but to a nonsignificant extent (t = study. LoE: 2−
LoE−1.1861). Thus the statistically
significant results reflect mild-to-
moderate improvement in
approximately half of the patients.
Analysis of the drop-outs not only
indicated suspiciousness and
SK Kirchner et al.
reluctance about taking any

medication but also repeated
complaints of side effects, even at
the 2 mg level of haloperidole
Goldberg ntotal = 50 (BPD 12-week Diagnosis of BPD and/or STPD Diagnosis of schizophrenia, mania, Thiothexine Drug-treated patients respond to Various
et al.48 and/or STPD) double-blind by DSM-III criteria (rated by and melancholia; severe hepatic, hydrocloride medication regardless of their MMPI outcomes.
placebo- Schedule for Interviewing renal, or cardiovascular disease; (mean dose profile. The MMPI scales validity (F), Monocentric
controlled trial Borderliners SIB), at least one organic brain symptom and/or 8.7 mg/day) depression (D), psychopathic deviate study. LoE: 2+
psychotic symptom mental retardation; history of (Pd), psychasthenia (Pt), paranoia
epilepsy or seizures; glaucoma; (Pa), and schizophrenia (Sc) are
current alcoholism or drug addiction; insufficient to predict outcome of
severe hypertensive or hypotensive drug response. The primary outcome
cardiovascular disease; severe variables of the same cohort
metabolic disorders measuring the drug–placebo
differences have already been
published in Goldberg et al. (1986)
Bogetto ntotal = 23 patients 12-week open- YBOCS score >16, HAMD score Major depressive disorder, dementia, Fluvoxamine Mean 11.5 ± 9.8 A significant decrease of mean No
et al.59 with non- label <5 (on the 17-item scale), delirium, amnestic or other cognitive (300 mg/day) duration of YBOCS score between pretreatment concealment.
responsive OCD, augmentation completion of Structured disorders; schizophrenia or other +augmentation illness (for and posttreatment 26.8 ± 3.0 vs. No
nSTPD = 4 trial (after Clinical Interview for DSM IV psychotic disorders and bipolar with olanzapine ntotal) 18.9 ± 5.9 was found at the end randomization.
6 month acute Personality Disorders (SCID-II), disorders; concomitant (5 mg/day) point. The rate of responders in the Various
treatment) ill for >1 year, completed an pharmacotherapy or psychotherapy; sample was 43.5%. Four of the 10 outcomes.
acute treatment phase, non- general medical condition that responders (40%) had a concomitant Monocentric
responder status would contraindicate the use of schizotypal personality disorder. study. LoE: 3
fluvoxamine or olanzapine None of the non-responders had a
schizotypal personality disorder. A

significant difference was found only
for the Axis II co-diagnosis (p =
0.024). Concomitant schizotypal
personality disorder was the only
9
10
Table 2 continued
(A) Antipsychotics
of bias LoE
according to
SIGN)
factor significantly associated with

response. It appears that
augmentation of olanzapine in
fluvoxamine-refractory OCD may be

effective in a large number of
patients, including those with
comorbid schizotypal personality
disorder
Mean YBOCS 26.8 ± 3.0 18.9 ± 5.9 Mean
score (for decrease:
ntotal) 8.0 ± 5.6
Koenigsberg nSTPD = 25 9-week Diagnosis of STPD by DSM-IV Diagnosis of schizophrenia, Low-dose PANSS total Reduction of Patients receiving active medication Various
et al.50 randomized, criteria rated by the Schedule schizophrenia-related psychotic risperidone 29% showed a significant decline of outcomes.
double-blind for Interviewing DSM-IV disorder, or bipolar disorder; (0.25–2 mg/day) symptoms (p < 0.05) on the PANSS Monocentric
placebo- Personality Disorders (SIDP-IV) comorbid borderline personality negative and general symptom study. LoE: 2++
controlled trial disorder; medical or neurological scales by week 3 and on the PANSS
illness; alcohol or substance abuse positive symptom scale by week 7
within the past 6 months or history compared with patients receiving
of past substance dependence; free placebo. PANSS scores at baseline
of psychotropic medication are not specifically mentioned and
only shown in figures (PANSS total ≈
60–70, PANSS negative ≈ 15–20,
PANSS general ≈ 30–35, PANSS
positive ≈ 15). Side effects were well
tolerated. There was no group
difference in drop-out rates.
Conclusion: Low-dose risperidone
SK Kirchner et al.
appears to be effective in reducing

symptom severity in STPD patients
and is generally well tolerated
PANSS Reduction of
negative 27%
PANSS Reduction of
general 30%
PANSS Reduction of
positive 27%
SPQ score 28.2 ± 17.4 19.6 ± 17.3 No significant
change
compared to
placebo
CGI 3.9 ± 1.2 3.0 ± 1.4 No significant
change
compared to
placebo
HAMD 10.5 ± 6.00 8.88 ± 6.79 No significant
change
compared to
placebo
Rybakowski ntotal = 8 (relatives Open study ntotal: first- or second-degree Manifested psychotic symptoms, Risperidone The continuous treatment with a No
et al.62 of schizophrenic relatives of schizophrenia previous pharmacologic treatment (0.5–2 mg/day) low-dose of risperidone concealment.
patients), nSTPD = patients; nSTPD: diagnosis of administered for 2 to 3 years resulted No
3 STPD by DSM-IV criteria, in a significant improvement in randomization.
impairment in social and social and occupational functioning Various
occupational functioning >1 and, in some of the subjects, in outcomes.
year spectacular educational and Monocentric
professional achievements. In the study. LoE: 3
subgroup of STPD patients, no side-
effects besides transient sleepiness
were reported. In 7 subjects,
neuropsychological tests were
obtained after 1 year of risperidone
treatment. In all of them, a highly
significant improvement compared

with pretreatment period was
observed on part B of Trail Making
Table 2 continued
(A) Antipsychotics
of bias LoE
according to
SIGN)
Test and part B of Stroop test as well

as on all the subtests of Wisconsin
Card Sorting Test
Keshavan nSTPD = 11 26-week open- Diagnosis of STPD based on Diagnosis of schizophrenia or Low-dose HRSD24 total 19.7 ± 6.9 11.9 ± 6.4 7.8 ± 8.4c Patients showed significant No
et al.60 label study Structured Clinical Interview schizoaffective disorder based on olanzapine improvements in psychosis and concealment.
for DSM-IV (SCID) SCID, previous neuroleptic treatment (average depression ratings, as well as in No
for STPD, significant medical or 9.32 mg/day) overall functioning. Olanzapine was randomization.
neurological illness, mental well tolerated, though significant Various
retardation, and pregnancy or weight gain was observed. outcomes.
lactation Conclusion: This study provides Monocentric
preliminary data regarding study. LoE: 3
olanzapine efficacy and tolerability
in schizotypal personality disorder
subjects. These data need to be
confirmed in larger controlled
clinical trials.c The change in
symptoms is measured as paired
difference between baseline and
posttreatment score
GAS 45.6 ± 11.5 59.6 ± 13.4 14.0 ± 9.0c
OAS 7.4 ± 5.6 2.1 ± 3.9 5.2 ± 6.0c
EPSE 0.65 ± 1.2 1.4 ± 2.2 0.75 ± 1.8
BPRS 18 total 44.8 ± 7.4 30.3 ± 7.8 −14.5 ± 7.5c
Di Lorenzo ntotal = 43 (17 Retrospective Diagnosis of schizophrenia- Aripiprazole BPRS (for 60.62 ± 4.73 44.81 ± 4.53 Improvement The final scores of the 2 scales Retrospective
et al.63 inpatients, 26 study spectrum disorder noutpatients) of 54% showed a statistically significant study. No
outpatients), difference from baseline (BPRS: p < concealment.
nSTPD = 1 0.001 in the 2 groups; GAF: p < 0.005 No

(inpatient) in inpatients, p = 0.001 in randomization.
outpatients). Inpatients and Various
outpatients could improve in BPRS outcomes.
and GAF. Specific effects for patients Monocentric
with STPD are not mentioned study. LoE: 3
BPRS (for 82.88 ± 5.13 56.65 ± 7.03 Improvement
ninpatients) of 71%
GAF (for 37.65 ± 2.70 51.27 ± 3.15 Improvement
SK Kirchner et al.
noutpatients) of 35%
GAF (for 30.29 ± 3.80 50.06 ± 5.69 Improvement
ninpatients) of 71%
McClure nSTPD = 31 2-week single- STPD diagnosis by Diagnostic The exclusion criteria are not Low-dose PANSS 26.9 ± 7.7 22.1 ± 5.2 There were no significant differences Various
et al.53 (respectively 20 blind lead-in, and Statistical Manual of specifically named risperidone general between the risperidone group and outcomes.
post drop-out) then 10 week Mental Disorders-Fourth (0.25–2 mg/day) the placebo group in change from Monocentric
double-blind, Edition criteria baseline in the PANSS or on any of study. LoE: 2++
randomized, the cognitive variables following
placebo- either 6 weeks, all Fs <0.5, all ps
controlled trial >0.15, or 12 weeks, all Fs <1.2, all ps
>0.28, of treatment
PANSS 11.9 ± 4.7 9.4 ± 2.5
positive
PANSS 13.9 ± 4.7 12.1 ± 5.2
negative
WMS-VR 33.1 ± 5.1 34.9 ± 7.1
WMS-VR LD 29.1 ± 8.4 36.8 ± 13.5
WLL trail 5 12.8 ± 5.3 15.7 ± 5.3
WLL LD 10.9 ± 4.2 15.7 ± 6.6
CPT d′ 0.9 ± 0.5 1.3 ± 0.83

PASAT 31.0 ± 5.9 36.7 ± 13.5
DOT 30 s 1.2 ± 1.4 0.91 ± 0.61

delay
O-LIFE (for 61.67 (9.41)
nSTPD)
11
12
Table 2 continued
(A) Antipsychotics
of bias LoE
according to
SIGN)
Rabella nSTPD = 9 Double-blind, Diagnosis of STPD using the Hospitalization or prior antipsychotic Risperidone SPQ score 44.67 (6.75) After placebo, STPD individuals Monocentic
et al.54 randomized, Spanish version of the treatment (1 mg/day) showed slower reaction times to hits, study. LoE: 2++
placebo- Structured Clinical Interview longer correction times following
controlled for the DSM-IV Axis II errors and reduced ERN and Pe

cross-over trial Personality Disorders (SCID-II) amplitudes. While risperidone
impaired performance and
decreased ERN and Pe in the control
group, it led to behavioral
improvements and ERN amplitude
increases in the STPD individuals.d
The symptom change is measured as
treatment × group interaction as
Cohen’s f
O-LIFE 61.67 (9.41)
Eriksen 1015 ± 197 F = 1.42d
Flanker Task:
total
responses
Eriksen 313 ± 88 F = 6.91d
Flanker Task:
RT corrected
errors
(B) Antidepressants
Markovitz ntotal = 22, 12-week, Diagnosis of BPD and/or STPD Psychopharmacological treatment Fluoxetine HSCL score 197.3 ± 60.1 69.5 ± 44.7 65% decrease Treatment with fluoxetine leads to No
et al.61 nSTPDonly = 4, prospective, by DSM-III-R criteria other than lorazepam and chloral (20–80 mg/day) (for ntotal) significant reduction in self-injury concealment.
SK Kirchner et al.
nSTPD+BPD = 10 open-label hydrate and Hopkins Symptom Checklist No

trial regardless of diagnosis randomization.
Various
outcomes.
Monocentric
study. LoE: 3
HSCL score 159.8 ± 39.6 52.5 ± 30.4
(for nSTPD)
HSCL score 206.8 ± 54.4 68.5 ± 29.4
(for
nSTPDandBPD)
Baer et al.46 ntotal = 55 patients 10-week YBOCS score ≥16; NIHM Global Relevant Axis I or II disorders that Clomipramine YBOCS (for 25.6 ± 6.7 No significant difference was noted No
with OCD, nSTPD double-blind Scale score ≥7; HAMD score may interfere with protocol hydrochloride ntotal) on either YBOCS (F = 1.1, df = 1.53, p randomization.
=5 placebo- ≤16 compliance 100–300 mg/day = 0.30) or NIHM Global Scale (F = 0.7, Various
controlled trial df = 1.53, p = 0.41) between patients outcomes. LoE:
with or without PD diagnoses at 2−
baseline. For Cluster A diagnoses,
there was a significant YBOCS main
effect (F = 6.2, df = 1.48, p = 0.02)
after the intervention. STPD showed
significant partial correlation with
YBOCS (r = 0.31, p < 0.02) and
significant Pearson's correlations
with PRAS (r = 0.28, p < 0.05)
YBOCS (for 32.4 ± 2.9 27.8 ± 7.6
nSTPD)
NIHM (for 9.7 ± 1.9
ntotal)
HAMD (for 5.4 ± 3.8
ntotal)
a
b
The symptom change is measured as standardized change: (pretreatment score−posttreatmentscore)/pretreatment standard deviation
c
The change in symptoms is measured as paired difference between baseline and posttreatment score
d
The symptom change is measured as treatment × group interaction as Cohen’s f

SK Kirchner et al.
13
Table 3. Qualitative synthesis of psychotherapy
Reference Study Study type Inclusion criteria Exclusion criteria Intervention Outcomea Level of
population evidence (risks
of bias LoE
according to
SIGN)
Karterud ntotal = 97, Non-blinded, Diagnosis of Axis Acute psychosis, 6-month psychodynamic The improvement of No
et al.69 nPD = 50, uncontrolled I or II psychiatric intense psychic day treatment including patients was measured by concealment.
nSTPD = 13 prospective disorder, for suffering with long- group psychotherapy (3× the change in symptoms No
trial nSTPD: diagnosis standing incapacity per week), art therapy (measured by General randomization.
according to to function in social groups (2× per week), body Symptom Index) and the Various
DSM-III-R criteria or family roles awareness group (2× per Global Functioning outcomes.
week), individual (measured by Health Monocentric
psychotherapy (1× per Sickness Rating Scale). study. LoE: 3
week), occupational therapy Whereas patients without
(1× per week) personality disorder
(change in GSI: 0.77 ± 0.50,
change in HSRS: 8.9 ± 6.9, p
< 0.01) improved the most,
followed by the BPD and
OCD groups, the
improvement for patients
with STPD was not
statistically significant
(change in GSI: 0.40 ± 0.77,
change in HSRS: 0.2 ± 7.1).
No patients committed
suicide. One STPD patient
made a suicidal attempt
and was temporarily
transferred to the acute
ward. One STPD patient
was transferred to long-
term psychiatric hospital
treatment
McKay nSTPD = 1 Case report Diagnosis of No criteria Social skills training plus The patient showed a Case report.
et al.70 with STPD by DSM-IV exposure with response decrease in OCD LoE: 3
comorbid assessed by prevention (ERP) symptomatology as
OCD SCID-II; diagnosis assessed by the YBOCS, as
of OCD by DSM- well as decreases in
III-R criteria depression and anxiety as
assessed by the Hamilton
Rating Scale for Depression
and the Hamilton Rating
Scale for Anxiety. This is
consistent with the
hypothesis that OCD, when
presented with comorbid
schizotypal personality, is
amenable to social skills
interventions. At 6-month
follow-up, the patient
continued to have
considerable symptoms,
although his level of
functioning had improved
and remained at
posttreatment levels
Nordentoft nSTPD = 79 Randomized Diagnosis of Overt psychotic Integrative vs. standard In the multivariate model, No
et al.68 clinical trial STPD by the symptoms treatment male gender increased risk concealment.
comparing research criteria for transition from STPD to Monocentric
integrated by the WHO psychotic disorder (relative study. LoE: 2
treatment with 1993 (ICD-10) risk = 4.47, (confidence
standard interval 1.30–15.33)), while
treatment integrated treatment
reduced the risk (relative
risk = 0.36 (confidence
interval 0.16–0.85)).
Significantly more patients
in integrated treatment
than in standard treatment
were treated with
antipsychotic medication.
Integrative treatment
included assertive
community treatment,
social skills training, family
involvement, and psycho-
education
a
SK Kirchner et al.
14
Table 4. Qualitative synthesis of longitudinal outcome studies of patients with schizotypal personality disorder
Reference Study population Follow-up period Outcomea
Plakun et al.71 ntotal = 237 psychiatric patients, 14 years Diagnoses in this study were based on DSM-III criteria. Patients suffering
nSTPD = 13, nSTPD+BPD = 6 from STPD without comorbid major affective disorder functioned better
than patients with SZ. They had higher scores in global functioning
(GAS) than SZ patients at baseline but not at follow-up. STPD patients
with comorbid BPD were as impaired as schizophrenics at admission but
significantly better at follow-up
McGlashan72 ntotal = 253 psychiatric patients, Range: 2–32 years STPD as defined by DSM-III criteria appeared to be common in the
nSTPD = 10, nSTPD+SZ = 61, nSTPD Chestnut Lodge follow-up study patients, although it was rare as a pure
+SZ+BPD = 30, nSTPD+BPD = 18 syndrome. From the perspective of follow-up, STPD seemed to be
related to SZ but not to BPD. The mixed Axis II borderline syndrome
(STPD+BPD) had a long-term profile closer to BPD than to STPD. The
cohorts meeting STPD criteria had relatively poor social adjustments
and fewer social contacts. The pure STPD cohort achieved the highest
level on education compared to the mixed diagnoses. The pure STPD
sample was mainly single (70%) and male (60%). Premorbid functioning
was poor socially and good instrumentally
Modestin et al.73 ntotal = 39 psychiatric patients, 4 years Diagnosis of STPD was based on DSM-III, of SZ on ICD-9 and parts on
nSTPD = 14 (7 for follow-up), nSZ DSM-III. A relationship not only between STPD and SZ but also between
= 25 (17 for follow-up) STPD and BPD could be detected. Pure STPD patients are rarely
dysfunctional and less likely to require hospital care. Therefore, the
clinical sample investigated is small and might not be representative for
all STPD patients. On a blind examination, STPD patients in this cohort
were found to be less socially adjusted and they tended to be more
symptomatic. Compared with a small DSM-III schizophrenia subgroup,
STPD patients undertook more suicide attempts. STPD patients were
rating higher in social dissatisfaction. Patients with STPD were more
anxious and they tended to suffer more from obsessive-compulsive
symptoms and depression. Transient psychoses were frequent in STPD
patients. The average neuroleptics dose was twice as low in STPD
compared to SZ (92% of ntotal received neuroleptic medication)
Mehlum et al.74 ntotal = 97 patients with PD, nSTPD range: 1.6–4.9 years STPD diagnoses were made according to DSM-III-R at index
= 13 at admission, nSTPD = 9 at hospitalization and by SCID interview at follow-up. STPD patients
discharge displayed a moderate symptom reduction after 3 years of treatment but
retained relatively poor global functioning. They were least socially
adjusted, employed, and self-supporting of all diagnostic subgroups.
STPD and BPD patients had far more inpatient treatment than other PDs
Bernstein et al.79 ntotal = 733 community-based 2 years The overall prevalence of personality disorders peaked at age 12 years in
adolescents boys and at age 13 years in girls and declined thereafter. STPD was the
least prevalent Axis II disorder (moderate STPD 1.8%, severe STPD 1.2%).
Children who met the criteria for STPD had increased social
impairments, school or work problems, and a higher comorbidity with
Axis I disorders. Longitudinal follow-up revealed that most Axis II
disorders did not persist over a 2-year period. Subjects with disorders
identified earlier remained at elevated risk for receiving a diagnosis
again at follow-up (persistence after 2 years: for moderate STPD 9%, for
severe STPD 11%)
Olin et al.80 ntotal = 232 children, nSTPD = 36 Range: 15–27 years, The lifetime diagnoses used in the study are based on DSM-III-R. The first
children based on teachers’ assessment was at age 15 years, the second at age 25 years, and the
school reports third between age 39 and 42 years. Those who later developed STPD
were found to be more passive and unengaged and more
hypersensitive to criticisms compared with the non-schizophrenia
groups according to school reports. Males who developed STPD were
found to be less disruptive and hyper-excitable compared with males
with schizophrenia; females with STPD did not differ from females with
schizophrenia. A receiver operating characteristic analysis found these
factors to predict 73.5% of future STPDs. The three major factors
accounting for 54.4% of the variance were labeled as “socially anxious
and withdrawn,” “disruptive and hyper-excitable,” and “passive and
unengaged.” These findings suggest that pre-schizotypal traits may be
identified in late childhood or adolescence
Comparative groups: ncomp1 = 31
SZ children, ncomp2 = 37
nonpsychotic but mentally ill
children, ncomp3 = 68 children not
mentally ill but schizophrenic
mother, ncomp4 = 60 healthy
children
Grilo et al.76 ntotal = 633 patients, nPD = 544, 2 years The study examined the stability of different personality disorders over
nMDD = 89, nSTPD = 78 time. The STPD remission rate was 61% after 24 months. Remission rates
after a more stringent definition with two or fewer criteria (by the
DSM–IV Personality Disorders Follow Along Version, DIPD-FAV) after 12
consecutive months was 23% for STPD. Dimensionally, these findings
suggest that PDs may be characterized by maladaptive trait
constellations that are stable in their structure (individual differences)
but can change in severity or expression over time
SK Kirchner et al.
15
Table 4 continued
Reference Study population Follow-up period Outcomea
Warner et al.77 ntotal = 376 patients with PD 2 years This study explores the extent to which relevant personality traits are
stable in individuals diagnosed with four personality disorders
(schizotypal, borderline, avoidant, and obsessive-compulsive personality
disorders). The PDQ-IV was used for screening. The DIPD-IV was used for
making the initial diagnosis based on DSM-IV criteria. The test–retest
kappa for STPD was 0.64. There was an insufficient sample size in the
inter-rater reliability sample to calculate the kappa for STPD, but
diagnostic agreement was 100%. Participants were interviewed at
6 months, 1 year, and 2 years following the baseline assessment.
Changes in personality traits were determined via a re-administration of
the NEO–PI–R at the 1- and 2-year follow-up. The DIPD–IV was modified
to record the presence of each criterion for the four PDs for each month
of the follow-up interval. The standardized parameter estimates
reflecting the stability for the latent trait variable across time were
significant and quite large (β= 0.76 and β = 0.83, both ps < 0.01) as were
the stability estimates for STPD (β = 0.90 and β = 0.81, both ps < 0.01).
The results demonstrate significant cross-lagged relationships between
trait change and later disorder change for three of the four personality
disorders studied
Asarnow et al.81 nSTPD = 12 children, nSZ = 18 range: 1–7 years There was significant continuity between SZ spectrum disorders in
children childhood and adolescence. The most common clinical outcome for
children with STPD was continuing STPD, supporting the hypothesis of
continuity between childhood and later STPD. However, 25% of the
STPD sample developed more severe SZ spectrum disorders
(schizophrenia or schizoaffective disorder, also supporting the
hypothesis that STPD represents a risk or precursor state for more severe
SZ spectrum disorders
McGlashan et al.78 ntotal = 474 patients with 2 years In this study, a 24-month follow-up was obtained to evaluate the change
personality disorders, nSTPD = 85 of personality disorder criteria over time. For STPD, the most prevalent
and least changeable criteria over 2 years were paranoid ideation, and
unusual experiences. The least prevalent and most changeable criteria
were odd behavior and constricted affect
Woods et al.82 n = 377 patients with prodromal 2.5 years 40% of prodromal patients converted to fully psychotic illness during 2.5
syndrome, nHSC = 196, nFHR = 40, years of follow-up. Corresponding rates for help-seeking comparison
NSTPD = 49 (HSC) group, familial high-risk (FHR) group, and STPD subjects were
correspondingly 4, 0, and 36%. Cox regression comparing distinguished
prodromal patients from HSC but not from STPD subjects
Debbane et al.24 n = 376 patients by a clinically range: 2–20 years The conversion rates from STPD to a psychotic disorder varied between
relevant expression of schizotypy 25% and 48%. Suspected STPD in children, however, seldom led to the
(i.e., STPD, schizoid PD, or SD later emergence of a schizophrenic-spectrum psychotic disorder (only
6.25%)
Kendler et al.20 ntotal = 2282 twins range: 6–11 years The study examines the stability of genetic and environmental factors in
paranoid and schizotypal PD. The stability over time of the criteria
counts for STPD, estimated as polychoric correlations, was +0.40. 71% of
the temporal stability derived from the effect of genetic factors. Shared
genetic risk factors for two of the Cluster A PDs are highly stable in
adults over a 10-year period while environmental risk factors are
relatively transient. Over two thirds of the long-term stability of the
common Cluster A PD liability can be attributed to genetic influences
a
In summary, our systematic review shows that the best the ENDNOTE X7 duplication detection feature. The publications
evidence for efficacy in STPD is available for risperidone and to (titles and abstracts) were then screened for relevance. To be
a limited extent for olanzapine. The literature on psychotherapy is included, the articles had to report on studies of original data and
sparse and does not allow us to make any recommendations, focus on the diagnosis, treatment, or follow-up of patients with
although social skills training seems to be effective and should be STPD. Because including only studies with a Scottish Intercollegi-
offered to patients with STPD. Large-scale naturalistic and ate Guidelines Network (SIGN) LoE of 1− to 1++ would have
interventional trials with defined diagnostic cohorts and strict limited the number of studies available for inclusion, we included
study designs are needed to provide the data for more detailed not only randomized control trials but also cohort studies,
evidence-based recommendations. retrospective non-analytical studies, and case studies (LoE 2++
to 3). Expert opinions (LoE 4) were not considered. Study designs
and LoE grading are described in the Tables 2A, B, and 3, and
METHODS Supplementary Tables 3 and 4. Reviews, meta-analyses, and non-
Study selection English publications were excluded. Two reviewers independently
This systematic review was conducted by searching the PubMed/ analyzed the full-text publications and retrieved data on clinical
MEDLINE databases for papers published at any time. We diagnosis and treatment. We searched also three additional
conducted the final search on September 14, 2016, at which time databases (WHO Clinical Trials (http://apps.who.int/trialsearch/),
the data source contained studies from April 1, 1947, to August 21, ClinicalTrials (https://clinicaltrials.gov/), and the Cochrane Library
2016. A total of 145 combinations of search terms were used to (http://www.cochranelibrary.com/)) for ongoing or planned clinical
search the databases with the ENDNOTE X7 search tools (see trials and for systematic reviews or meta-analyses. Using the
Supplementary Information). Duplicates were removed by using search term “schizotypal personality disorder,” we identified 18
SK Kirchner et al.
16
clinical trials. Furthermore, we found two additional trials that had Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims
been completed; however, upon closer inspection it became clear in published maps and institutional affiliations.
that they did not meet the inclusion criteria for this systematic
review. We identified one protocol83 in the Cochrane Library, but it
was withdrawn with no results in 2014. REFERENCES
Our search strategy yielded 3420 unique studies, 3326 of which 1. Raine, A. Schizotypal personality: neurodevelopmental and psychosocial trajec-
were excluded after we had screened the titles, abstracts, and tories. Annu. Rev. Clin. Psychol. 2, 291–326 (2006).
2. Fonseca-Pedrero, E. et al. The structure of schizotypal personality traits: a cross-
article format reviews, resulting in 94 full-text articles. These 94
national study. Psychol. Med. 48, 451–462 (2018).
articles were scanned for the inclusion criteria of this systematic 3. Kwapil, T. R., Barrantes-Vidal, N. & Silvia, P. J. The dimensional structure of the
review—to be included, studies had to investigate diagnostic Wisconsin Schizotypy Scales: factor identification and construct validity. Schi-
instruments for or the treatment or longitudinal course of STPD. zophr. Bull. 34, 444–457 (2008).
After full-text screening, 38 articles had to be excluded because 4. Kwapil, T. R., Gross, G. M., Silvia, P. J., Raulin, M. L. & Barrantes-Vidal, N. Devel-
they did not include original data or were not about clinical opment and psychometric properties of the Multidimensional Schizotypy Scale: a
patients with STPD. The remaining 56 articles were sorted into the new measure for assessing positive, negative, and disorganized schizotypy.
following categories: clinical diagnostic instruments (18 studies), Schizophr. Res. 193, 209–217 (2018).
pharmacological treatment (22 studies), psychotherapy (3 studies), 5. Mason, O. J. The assessment of schizotypy and its clinical relevance. Schizophr.
Bull. 41(Suppl 2), S374–S385 (2015).
and longitudinal course and follow-up (13 studies) (see Supple-
6. Meehl, P. E. Schizotaxia, schizotypy, schizophrenia. Arch. Gen. Psychiatry 46,
mentary Information). Publications on diagnostic questionnaires 935–944 (1962).
were only included if they evaluated diagnostic criteria or 7. Meehl, P. E. Toward an integrated theory of schizotaxia. J. Pers. Disord. 4, 1–99
questionnaires as assessment tools. Articles on factor analysis (1990).
models alone were excluded, and publications on drug treatment 8. Lenzenweger, M. F. Schizotypy, schizotypic psychopathology and schizophrenia.
were excluded if there was no report of a clinical outcome. We World Psychiatry 17, 25–26 (2018).
identified three overlapping patient cohorts: one in the articles on 9. Chapman, L. J. et al. Impulsive nonconformity as a trait contributing to the
diagnostic instruments (Battaglia et al.35 and Fossati et al.44); one prediction of psychotic-like and schizotypal symptoms. J. Nerv. Ment. Dis. 172,
in the articles on drug treatment (Goldberg et al. 198647 and 681–691 (1984).
10. Kwapil, T. R. & Barrantes-Vidal, N. Schizotypy: looking back and moving forward.
198748); and one in the Chestnut Lodge cohort (McGlashan et al.
Schizophr. Bull. 41(Suppl 2), S366–S373 (2015).
published an article on testing DSM-III criteria29 and a 2-year 11. Ettinger, U., Meyhofer, I., Steffens, M., Wagner, M. & Koutsouleris, N. Genetics,
follow-up study in a separate article72). cognition, and neurobiology of schizotypal personality: a review of the overlap
with schizophrenia. Front. Psychiatry 5, 18 (2014).
General study characteristics 12. Fonseca-Pedero, E. D. M. Schizotypal traits and psychotic-like experiences during
adolescence: an update. Psicothema 29, 5–17 (2017).
We assumed a large heterogeneity in disease severity among the 13. Fanous, A. H. et al. Significant correlation in linkage signals from genome-wide
included patients who were recruited in outpatient and inpatient scans of schizophrenia and schizotypy. Mol. Psychiatry 12, 958–965 (2007).
settings. Because of the inconsistent outcome measures in the 14. Walter, E. E., Fernandez, F., Snelling, M. & Barkus, E. Genetic consideration of
interventional groups, in our view the available data were not schizotypal traits: a review. Front. Psychol. 7, 1769 (2016).
suited to perform quantitative analyses, e.g., with a meta- 15. Gaebel, W., Zielasek, J. & Cleveland, H. R. Classifying psychosis--challenges and
analytical approach. Some study populations included also opportunities. Int. Rev. Psychiatry 24, 538–548 (2012).
healthy and population-based individuals, but these studies were 16. World Health Organization. The ICD-10 classification of mental and behavioural
only taken into consideration when a clinical diagnosis of STPD disorders: clinical descriptions and diagnostic guidelines (World Health Organiza-
tion, 2016) http://www.who.int/classifications/icd/en/bluebook.pdf.
was mentioned.20,34,36,38,79,80 Most of the studies focused on
17. Pulay, A. J. et al. Prevalence, correlates, disability, and comorbidity of DSM-IV
adults, although three focused on children and the longitudinal schizotypal personality disorder: results from the wave 2 national epidemiologic
course of their diseases.79–81 The study sizes varied greatly, as survey on alcohol and related conditions. Prim. Care. Companion J. Clin. Psychiatry
indicated in Supplementary Table 2. 11, 53–67 (2009).
18. Rosell, D. R., Futterman, S. E., McMaster, A. & Siever, L. J. Schizotypal personality
disorder: a current review. Curr. Psychiatry Rep. 16, 452 (2014).
DATA AVAILABILITY 19. Sobin, C. et al. Evidence of a schizotypy subtype in OCD. J. Psychiatr. Res. 34,
This is a systematic review. All data generated or analyzed during this study is 15–24 (2000).
included in this published article (or Supplementary Information). No other data are 20. Kendler, K. S. et al. A longitudinal twin study of cluster A personality disorders.
available. Psychol. Med. 45, 1531–1538 (2015).
21. Bilder, R. M. et al. Neurocognitive correlates of the COMT Val(158)Met poly-
morphism in chronic schizophrenia. Biol. Psychiatry 52, 701–707 (2002).
ACKNOWLEDGEMENTS 22. Nyegaard, M. et al. CACNA1C (rs1006737) is associated with schizophrenia. Mol.
Psychiatry 15, 119–121 (2010).
The authors thank Jacquie Klesing, Board-certified Editor in the Life Sciences (ELS), for
23. Hodgkinson, C. A. et al. Disrupted in schizophrenia 1 (DISC1): association with
editing assistance with the manuscript.
schizophrenia, schizoaffective disorder, and bipolar disorder. Am. J. Hum. Genet.
75, 862–872 (2004).
24. Debbane, M. et al. Developing psychosis and its risk states through the lens of
AUTHOR CONTRIBUTIONS schizotypy. Schizophr. Bull. 41(Suppl 2), S396–S407 (2015).
S.K.K. and A.H. designed the study. S.K.K. searched the literature. S.K.K. and A.R. 25. Herpertz, S. C. et al. World Federation of Societies of Biological Psychiatry (WFSBP)
extracted the data, and A.H. and J.N. reviewed it. All authors wrote and approved the guidelines for biological treatment of personality disorders. World J. Biol. Psy-
manuscript. chiatry 8, 212–244 (2007).
26. Moher, D., Liberati, A., Tetzlaff, J., Altman, D. G. & Group, P. Preferred reporting
items for systematic reviews and meta-analyses: the PRISMA statement. Ann.
ADDITIONAL INFORMATION Intern. Med. 151, 264–269 (2009). W264.
Supplementary information accompanies the paper on the npj Schizophrenia 27. Jacobsberg, L. B., Hymowitz, P., Barasch, A. & Frances, A. J. Symptoms of schi-
website (https://doi.org/10.1038/s41537-018-0062-8). zotypal personality disorder. Am. J. Psychiatry 143, 1222–1227 (1986).
28. Widiger, T. A., Frances, A., Warner, L. & Bluhm, C. Diagnostic criteria for the
Competing interests: In the past 5 years, A.H. received a paid speakership from borderline and schizotypal personality disorders. J. Abnorm. Psychol. 95, 43–51
Desitin, Otsuka, Janssen-Cilag, and Lundbeck. He was previously member of an (1986).
advisory boards of Roche, Otsuka, Lundbeck, and Janssen-Cilag. The authors declare 29. McGlashan, T. H. Testing DSM-III symptom criteria for schizotypal and borderline
no competing interests. personality disorders. Arch. Gen. Psychiatry 44, 143–148 (1987).
SK Kirchner et al.
17
30. Vaglum, P., Friis, S., Vaglum, S. & Larsen, F. Comparison between personality 57. Serban, G. & Siegel, S. Response of borderline and schizotypal patients to small
disorder diagnoses in DSM-III and DSM-III-R: reliability, diagnostic overlap, pre- doses of thiothixene and haloperidol. Am. J. Psychiatry 141, 1455–1458 (1984).
dictive validity. Psychopathology 22, 309–314 (1989). 58. Hymowitz, P., Frances, A., Jacobsberg, L. B., Sickles, M. & Hoyt, R. Neuroleptic
31. Handest, P. & Parnas, J. Clinical characteristics of first-admitted patients with ICD- treatment of schizotypal personality disorders. Compr. Psychiatry 27, 267–271
10 schizotypal disorder. Br. J. Psychiatry Suppl. 48, s49–s54 (2005). (1986).
32. Perry, J. C., O’Connell, M. E. & Drake, R. An assessment of the schedule for schi- 59. Bogetto, F., Bellino, S., Vaschetto, P. & Ziero, S. Olanzapine augmentation of
zotypal personalities and the DSM-III criteria for diagnosing schizotypal person- fluvoxamine-refractory obsessive-compulsive disorder (OCD): a 12-week open
ality disorder. J. Nerv. Ment. Dis. 172, 674–680 (1984). trial. Psychiatry Res. 96, 91–98 (2000).
33. Stangl, D., Pfohl, B., Zimmerman, M., Bowers, W. & Corenthal, C. A structured 60. Keshavan, M., Shad, M., Soloff, P. & Schooler, N. Efficacy and tolerability of
interview for the DSM-III personality disorders. A preliminary report. Arch. Gen. olanzapine in the treatment of schizotypal personality disorder. Schizophr. Res.
Psychiatry 42, 591–596 (1985). 71, 97–101 (2004).
34. Raine, A. The SPQ: a scale for the assessment of schizotypal personality based on 61. Markovitz, P. J., Calabrese, J. R., Schulz, S. C. & Meltzer, H. Y. Fluoxetine in the
DSM-III-R criteria. Schizophr. Bull. 17, 555–564 (1991). treatment of borderline and schizotypal personality disorders. Am. J. Psychiatry
35. Battaglia, M., Cavallini, M. C., Macciardi, F. & Bellodi, L. The structure of DSM-III-R 148, 1064–1067 (1991).
schizotypal personality disorder diagnosed by direct interviews. Schizophr. Bull. 62. Rybakowski, J. K., Drozdz, W. & Borkowska, A. Low dose risperidone in the
23, 83–92 (1997). treatment of schizophrenia-like symptoms in high-risk subjects. J. Clin. Psycho-
36. Merritt, R. D., Balogh, D. W. & Kok, C. J. DSM-IV Cluster A personality disorder pharmacol. 23, 674–675 (2003).
diagnoses among young adults with a 2-7-8 MMPI profile. Assessment 5, 273–285 63. Di Lorenzo, R. et al. Aripiprazole: effectiveness and safety under naturalistic
(1998). conditions. Exp. Clin. Psychopharmacol. 15, 569–575 (2007).
37. Fossati, A. et al. Latent class analysis of DSM-IV schizotypal personality disorder 64. Gutkovich, Z., Rosenthal, R. N. & Bogdonoff, L. Transient psychosis with psycho-
criteria in psychiatric patients. Schizophr. Bull. 27, 59–71 (2001). genic polydipsia in schizotypal patient taking fluoxetine. Psychosomatics 39,
38. Dickey, C. C. et al. Clinical, cognitive, and social characteristics of a sample of 295–296 (1998).
neuroleptic-naive persons with schizotypal personality disorder. Schizophr. Res. 65. Heiden, A., de Zwaan, M., Frey, R., Presslich, O. & Kasper, S. Paroxetine in a patient
78, 297–308 (2005). with obsessive-compulsive disorder, anorexia nervosa and schizotypal person-
39. Morey, L. C., Benson, K. T. & Skodol, A. E. Relating DSM-5 section III personality ality disorder. J. Psychiatry Neurosci. 23, 179–180 (1998).
traits to section II personality disorder diagnoses. Psychol. Med. 46, 647–655 66. Poyurovsky, M. Clozapine in treatment-refractory obsessive-compulsive disorder
(2016). with comorbid schizotypal personality disorder. Isr. J. Psychiatry Relat. Sci. 45,
40. Sanislow, C. A. et al. Confirmatory factor analysis of DSM-IV borderline, schizo- 219–220 (2008).
typal, avoidant and obsessive-compulsive personality disorders: findings from the 67. Zwier, K. J. & Rao, U. Buspirone use in an adolescent with social phobia and mixed
Collaborative Longitudinal Personality Disorders Study. Acta Psychiatr. Scand. personality disorder (cluster A type). J. Am. Acad. Child Adolesc. Psychiatry 33,
105, 28–36 (2002). 1007–1011 (1994).
41. McGlashan, T. H. Recovery style from mental illness and long-term outcome. J. 68. Nordentoft, M. et al. Transition rates from schizotypal disorder to psychotic dis-
Nerv. Ment. Dis. 175, 681–685 (1987). order for first-contact patients included in the OPUS trial. A randomized clinical
42. Axelrod, S. R., Grilo, C. M., Sanislow, C. & McGlashan, T. H. Schizotypal Personality trial of integrated treatment and standard treatment. Schizophr. Res. 83, 29–40
Questionnaire-Brief: factor structure and convergent validity in inpatient ado- (2006).
lescents. J. Pers. Disord. 15, 168–179 (2001). 69. Karterud, S. et al. Day hospital therapeutic community treatment for patients with
43. Ryder, A. G., Costa, P. T. & Bagby, R. M. Evaluation of the SCID-II personality personality disorders. An empirical evaluation of the containment function. J.
disorder traits for DSM-IV: coherence, discrimination, relations with general Nerv. Ment. Dis. 180, 238–243 (1992).
personality traits, and functional impairment. J. Pers. Disord. 21, 626–637 (2007). 70. McKay, D. & Neziroglu, F. Social skills training in a case of obsessive-compulsive
44. Fossati, A. et al. Taxonic structure of schizotypal personality disorder: a multiple- disorder with schizotypal personality disorder. J. Behav. Ther. Exp. Psychiatry 27,
instrument, multi-sample study based on mixture models. Psychiatry Res. 137, 189–194 (1996).
71–85 (2005). 71. Plakun, E. M., Burkhardt, P. E. & Muller, J. P. 14-year follow-up of borderline and
45. Matsui, M., Sumiyoshi, T., Niu, L., Kurokawa, K. & Kurachi, M. Minnesota Multi- schizotypal personality disorders. Compr. Psychiatry 26, 448–455 (1985).
phasic Personality Inventory profile characteristics of schizotypal personality 72. McGlashan, T. H. Schizotypal personality disorder. Chestnut Lodge follow-up
disorder. Psychiatry Clin. Neurosci. 56, 443–452 (2002). study: VI. Long-term follow-up perspectives. Arch. Gen. Psychiatry 43, 329–334
46. Baer, L. et al. Effect of axis II diagnoses on treatment outcome with clomipramine (1986).
in 55 patients with obsessive-compulsive disorder. Arch. Gen. Psychiatry 49, 73. Modestin, J., Foglia, A. & Toffler, G. Comparative study of schizotypal and schi-
862–866 (1992). zophrenic patients. Psychopathology 22, 1–13 (1989).
47. Goldberg, S. C. et al. Borderline and schizotypal personality disorders treated with 74. Mehlum, L. et al. Personality disorders 2-5 years after treatment: a prospective
low-dose thiothixene vs placebo. Arch. Gen. Psychiatry 43, 680–686 (1986). follow-up study. Acta Psychiatr. Scand. 84, 72–77 (1991).
48. Goldberg, S. C., Schulz, S. C., Resnick, R. J., Hamer, R. M. & Schulz, P. M. Differential 75. Bender, D. S. et al. Treatment utilization by patients with personality disorders.
prediction of response to thiothixene and placebo in borderline and schizotypal Am. J. Psychiatry 158, 295–302 (2001).
personality disorders. Psychopharmacol. Bull. 23, 342–346 (1987). 76. Grilo, C. M. et al. Two-year stability and change of schizotypal, borderline, avoi-
49. Kirrane, R. M., Mitropoulou, V., Nunn, M., Silverman, J. & Siever, L. J. Physostigmine dant, and obsessive-compulsive personality disorders. J. Consult. Clin. Psychol. 72,
and cognition in schizotypal personality disorder. Schizophr. Res. 48, 1–5 (2001). 767–775 (2004).
50. Koenigsberg, H. W. et al. Risperidone in the treatment of schizotypal personality 77. Warner, M. B. et al. The longitudinal relationship of personality traits and dis-
disorder. J. Clin. Psychiatry 64, 628–634 (2003). orders. J. Abnorm. Psychol. 113, 217–227 (2004).
51. McClure, M. M. et al. The effects of guanfacine on context processing abnorm- 78. McGlashan, T. H. et al. Two-year prevalence and stability of individual DSM-IV
alities in schizotypal personality disorder. Biol. Psychiatry 61, 1157–1160 (2007). criteria for schizotypal, borderline, avoidant, and obsessive-compulsive person-
52. McClure, M. M. et al. Pergolide treatment of cognitive deficits associated with ality disorders: toward a hybrid model of axis II disorders. Am. J. Psychiatry 162,
schizotypal personality disorder: continued evidence of the importance of the 883–889 (2005).
dopamine system in the schizophrenia spectrum. Neuropsychopharmacology 35, 79. Bernstein, D. P. et al. Prevalence and stability of the DSM-III-R personality dis-
1356–1362 (2010). orders in a community-based survey of adolescents. Am. J. Psychiatry 150,
53. McClure, M. M. et al. The effects of risperidone on the cognitive performance of 1237–1243 (1993).
individuals with schizotypal personality disorder. J. Clin. Psychopharmacol. 29, 80. Olin, S. S. et al. Childhood behavior precursors of schizotypal personality disorder.
396–398 (2009). Schizophr. Bull. 23, 93–103 (1997).
54. Rabella, M. et al. Neurophysiological evidence of impaired self-monitoring in 81. Asarnow, J. R. Childhood-onset schizotypal disorder: a follow-up study and
schizotypal personality disorder and its reversal by dopaminergic antagonism. comparison with childhood-onset schizophrenia. J. Child Adolesc. Psycho-
Neuroimage Clin. 11, 770–779 (2016). pharmacol. 15, 395–402 (2005).
55. Rosell, D. R. et al. Effects of the D1 dopamine receptor agonist dihydrexidine 82. Woods, S. W. et al. Validity of the prodromal risk syndrome for first psychosis:
(DAR-0100A) on working memory in schizotypal personality disorder. Neu- findings from the North American Prodrome Longitudinal Study. Schizophr. Bull.
ropsychopharmacology 40, 446–453 (2015). 35, 894–908 (2009).
56. Siegel, B. V. et al. D-amphetamine challenge effects on Wisconsin Card Sort Test. 83. Farooq, S., et al. Pharmacological interventions for schizotypal personality dis-
Performance in schizotypal personality disorder. Schizophr. Res. 20, 29–32 (1996). order. Cochrane Database Syst. Rev. CD009047 (2011).
SK Kirchner et al.
18
Open Access This article is licensed under a Creative Commons article’s Creative Commons license and your intended use is not permitted by statutory
Attribution 4.0 International License, which permits use, sharing, regulation or exceeds the permitted use, you will need to obtain permission directly
adaptation, distribution and reproduction in any medium or format, as long as you give from the copyright holder. To view a copy of this license, visit http://creativecommons.
appropriate credit to the original author(s) and the source, provide a link to the Creative org/licenses/by/4.0/.
Commons license, and indicate if changes were made. The images or other third party
material in this article are included in the article’s Creative Commons license, unless
indicated otherwise in a credit line to the material. If material is not included in the © The Author(s) 2018

Jurnal Skizotipal 3

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Jurnal Skizotipal 3

Uploaded by

Copyright:

Available Formats

www.nature.

REVIEW ARTICLE OPEN

Diagnosis and treatment of schizotypal personality disorder:

INTRODUCTION Since the introduction of the diagnosis of STPD in Diagnostic

Received: 5 November 2017 Revised: 15 August 2018 Accepted: 21 August 2018

Published in partnership with the Schizophrenia International Research Society

Reference Study population Questionnaire Outcomea

Published in partnership with the Schizophrenia International Research Society

compared to other personality disorders: inadequate rapport (φ = 0.61), odd

npj Schizophrenia (2018) 20

discriminating symptoms are illusions/depersonalisation/derealisation. Whereas

npj Schizophrenia (2018) 20

Published in partnership with the Schizophrenia International Research Society

interpersonal deﬁcits, and disorganization. The SBQ-B shows adequate internal

Published in partnership with the Schizophrenia International Research Society

npj Schizophrenia (2018) 20

coherence, discrimination, relations with personality traits, and functional impairments.

demonstrated substantial correlations with the corresponding DSM‐IV diagnoses, with

roughly comparable with DSM-IV criterion-derived diagnoses with the κs (median κ =

schizotypal personality disorder include three traits of the psychoticism domain

relation to personality dimension of 0.18, and a relation to impairment of 0.36.

assignments speciﬁed for personality disorders in the DSM-5 alternative model

(cognitive and perceptual dysregulation, unusual beliefs and experiences, and

Model of Personality dimensions, suggesting that it may be a candidate for

eccentricity), which demonstrated correlations between 0.67 and 0.61

Individual outcomes. Most of the studies on an antipsychotic

found no beneﬁcial effect of risperidone in either the PANSS or

patients with STPD had signiﬁcant improvements in psychosis and

effects, i.e., it reduced the YBOCS score,59 and the concomitant

Assessment of Functioning (GAF)

Personality Inventory for DSM-5

diagnosis of STPD was signiﬁcantly associated with a positive

response. In a retrospective study, Di Lorenzo et al. reported a

decrease of general symptoms when patients with schizophrenia

patient with comorbid OCD and STPD.66 Three studies investigat-

Studies evaluating antidepressant treatment examined only

Table 2B). In an open-label trial of ﬂuoxetine, Markovitz et al.

measured a reduction of general symptoms in patients with BPD,

a worse treatment outcome in patients with comorbid STPD than

treatment with ﬂuoxetine,64 and other case reports showed

Sorting Test (WCST); however, the authors found no effect of

dopamine agonists (pergolide and dihydrexidine) and showed

ing, information processing, and divided attention.52,55 Two

npj Schizophrenia (2018) 20

Published in partnership with the Schizophrenia International Research Society

Psychoticism 1.14 0.36 0.73b

Published in partnership with the Schizophrenia International Research Society

reluctance about taking any

npj Schizophrenia (2018) 20

factor signiﬁcantly associated with

npj Schizophrenia (2018) 20

appears to be effective in reducing

Published in partnership with the Schizophrenia International Research Society

Test and part B of Stroop test as well

Published in partnership with the Schizophrenia International Research Society

CPT d′ 0.9 ± 0.5 1.3 ± 0.83

npj Schizophrenia (2018) 20

npj Schizophrenia (2018) 20

nSTPD+BPD = 10 open-label hydrate and Hopkins Symptom Checklist No

Published in partnership with the Schizophrenia International Research Society

Reference Study population Follow-up period Outcomea

You might also like